Résumé :
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In Duchenne Muscular Dystrophy (DMD) the selective removal by exon skipping of exons flanking an out-of frame mutation in the dystrophin messenger can result in in-frame mRNA transcripts that are translated into shorter but functionally active dystrophin.In 7 Golden Retriever Muscular Dystrophy (GRMD) dogs, a recombinant Adeno-Associated Virus serotype 8 (rAAV8) expressing a optimized U7 snRNA specific for the correction by exon skipping of the GRMD dystrophin transcript has been delivered by locoregional high-pressure intravenous (IV) injection of a forelimb. Tree months later, all the forelimb muscles (32) and 14 others muscles were sampled and analyzed. Depending on the different rAAV8-U7snRNA doses (2,5E12 to 2,5E13 vg/kg) and on the muscles, percentages of dystrophin positive fibers varied from 0 to 92 %. Intramuscular distribution and localization of the positive fibers will be presented.This project is supported by AFM (Association Franse contre les Myopathies) and by ADNA (Advanced Diagnostics for New Therapeutic Approaches), a program dedicated to personalized medicine, coordinated by Institut Meux and supported by research and innovation aid from the French public agency, OSEO
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